Searching for Bacterial Biofilm in Recurrent Cholangitis in Primary Sclerosing Cholangitis:A Case Presentation and Introduction of an Unexplored Disease Mechanism

Inflammation and fibrosis of the bile ducts are the defining pathological characteristics of primary sclerosing cholangitis(PSC).A previously unexplored mechanism for recurrent cholangitis,one of PSC's most common presentations,is bacterial colonization of the biliary epithelium in the form of biofilm,which may confer resistance to antibiotics and host phagocytic machinery.The aim of the current study was to assess whether bacteria could be seen on the liver explant and whether they organized in the form of biofilm.An explanted PSC liver from a 60-year-old male who suffered from recurrent cholangitis was formalin-fixed,paraffinembedded and Gram stained.The specimens were observed under light microscopy.Neither bacteria nor biofilm were detected.We did not detect bacteria or biofilm in the liver explant of a single PSC patient with recurrent cholangitis using standard light microscopy.We suspect this may be in part due to techniques related to tissue preservation and microscopy.

Effects of epidermal growth factor receptor inhibitor on proliferative cholangitis in hepatolithiasis

BACKGROUND： There is currently no effective medication to prevent stone recurrence after choledochoscopic lithotomy or to treat proliferative cholangitis（PC）, which is the pathologic basis of hepatolithiasis. This study aimed to investigate whether gefitinib, an epidermal growth factor receptor（EGFR） inhibitor, inhibited cholangio hyperplasia and lithogenesis in PC.METHODS： After cholangioscopic lithotomy, indwelling catheters were placed in the diseased bile duct lumens in 94 patients with hepatolithiasis. Subsequently, 49 of the 94 patients were treated with 250 mg gefitinib solution via a catheter twice a week, and they were subjected to choledochoscopic biopsy at 6 and 12 weeks. The rest 45 hepatolithiasis patients without gefitinib treatment served as controls.RESULTS： The expressions of EGFR, PCNA and procollagen I were significantly reduced in the patients treated with gefitinib in 12 weeks compared with those in the control group. Patients in the gefitinib group had a much lower degree of hyperplasia of the biliary epithelium, submucosal glands and collagen fibers compared with those in the control group. Gefitinib treatment significantly decreased mucin 3 expression and β-glucuronidase activity.CONCLUSION： Postoperative gefitinib treatment could significantly inhibit PC-mediated hyperplasia and lithogenesis, which might provide a novel strategy for the prevention of biliary restenosis and stone recurrence in patients with hepatolithiasis.

Hepatolithiasis:Epidemiology,presentation,classification and management of a complex disease

The term hepatolithiasis describes the presence of biliary stones within the intrahepatic bile ducts,above the hilar confluence of the hepatic ducts.The disease is more prevalent in Asia,mainly owing to socioeconomic and dietary factors,as well as the prevalence of biliary parasites.In the last century,owing to migration,its global incidence has increased.The main pathophysiological mechanisms involve cholangitis,bile infection and biliary strictures,creating a self-sustaining cycle that perpetuates the disease,frequently characterised by recurrent episodes of bacterial infection referred to as syndrome of“recurrent pyogenic cholangitis”.Furthermore,long-standing hepatolithiasis is a known risk factor for development of intrahepatic cholangiocarcinoma.Various classifications have aimed at providing useful insight of clinically relevant aspects and guidance for treatment.The management of symptomatic patients and those with complications can be complex,and relies upon a multidisciplinary team of hepatologists,endoscopists,interventional radiologists and hepatobiliary surgeons,with the main goal being to offer relief from the clinical presentations and prevent the development of more serious complications.This comprehensive review provides insight on various aspects of hepatolithiasis,with a focus on epidemiology,new evidence on pathophysiology,most important clinical aspects,different classification systems and contemporary management.

Complicated course of biliary inflammatory myofibroblastic tumor mimicking hilar cholangiocarcinoma:A case report and literature review

BACKGROUND The inflammatory myofibroblastic tumor(IMT)is a rare,idiopathic,usually benign,mass-forming disease with myofibroblastic proliferation and a varying amount of inflammatory cells.Although it can affect various organs,the biliary tract is a rare localization of primary IMT,clinically,endoscopically and radiologically imitating cholangiocarcinoma.The treatment options are based only on clinical practice experience.CASE SUMMARY A 70-year-old woman was referred to our center due to progressive fatigue,weight loss,abdominal pain,night sweats,and elevated liver enzymes.Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography(ERCP)revealed proximal common hepatic duct and hilar biliary strictures extending bilaterally to lobular bile ducts.Although initial clinical,endoscopic and radiological signs were typical for hilar cholangiocarcinoma,histological examination showed no signs of malignancy.In total,8 biopsies using different approaches were performed(several biopsies from dominant stricture during ERCP and direct cholangioscopy;ultrasound-guided liver biopsy;diagnostic laparoscopy with liver and lymph node biopsies).Histological examination revealed signs of IMT,and the final diagnosis of biliary IMT was stated.Although IMT is usually a benign disease,in our case,it was complicated.All pharmacological treatment measures were ineffective.The patient still needs permanent stenting,suffers from recurrent infections and mechanical jaundice.Despite that,the patient already survived 24 mo.CONCLUSION IMT presenting with hilar biliary strictures is a unique diagnostic and clinical challenge as it is indistinguishable from cholangiocarcinoma,and there are no evidence-based treatment options.Our goal is to increase the understanding of this rare disease and its possible course.